RESUMEN
The central route of streptozotocin (STZ) administration has been introduced as a rat model of sporadic Alzheimer's disease (AD). Curcumin was suggested to possess possible neuroprotective effects, which may be profitable in AD. However, the low bioavailability of curcumin hinders its beneficial effects in clinical studies. Earlier studies suggested that a bovine serum albumin-based nanocurcumin, produces superior neuroprotective effects compared to natural curcumin. In the present study, the protective effect of nanocurcumin in rat model of central STZ induced memory impairment was assessed. In addition, due to the importance of the hippocampus in memory, the amounts of hippocampal active caspase-3, Akt, and CaMKII-α were evaluated. Adult male Wistar rats weighing 250-300â¯g were used. STZ (icv) was injected during days 1 and 3 (3â¯mg/kg in divided), and nanocurcumin or curcumin 50â¯mg/kg/oral gavage was administered daily during days 4-14. Morris water maze training was performed on days 15-17, and the retention memory test was achieved on the 18th day. Following memory assessment, the rats were sacrificed and the hippocampi were used to assess caspase-3 cleavage, Akt, and CaMKII-α signaling. The findings revealed that nanocurcumin ingestion (but not natural curcumin) in the dose of 50â¯mg/kg was capable to prevent the impairment of water maze learning and memory induced by central STZ. Molecular assessments indicated that STZ treatment increased the caspase-3 cleavage in the hippocampus while deactivating Akt and CaMKII-α. Nanocurcumin reduced caspase-3 cleavage to a non-significant level compared to control group and restored Akt and CaMKII-α within the hippocampus while natural curcumin exerted no significant effect. These findings might suggest that nanocurcumin can restore memory deficit, hippocampal apoptosis as well as Akt and CaMKII-α signaling disruption associated with brain insulin resistance.
Asunto(s)
Enfermedad de Alzheimer , Apoptosis , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Curcumina , Modelos Animales de Enfermedad , Hipocampo , Trastornos de la Memoria , Fármacos Neuroprotectores , Proteínas Proto-Oncogénicas c-akt , Ratas Wistar , Transducción de Señal , Estreptozocina , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Curcumina/farmacología , Curcumina/administración & dosificación , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/prevención & control , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estreptozocina/farmacología , Ratas , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Apoptosis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Transducción de Señal/efectos de los fármacos , Caspasa 3/metabolismoRESUMEN
OBJECTIVES: Increasing evidence indicates a link between aluminum (Al) intake and Alzheimer's disease (AD). The main entry of Al into the human body is through oral route, and in the digestive tract, under the influence of the pH change, Al can be transformed into Al nanoparticles (Al-NP). However, studies related to the effect of Al-NP on the brain are limited and need further investigation. Neuro-inflammation is considered as one of the principal features of AD. Microglial activation and expression of the inflammatory cytokine IL-1ß (interleukin-1ß) in the brain have been used as hallmarks of brain inflammation. Therefore, in the present study, the hippocampal levels of ionized calcium-binding adaptor molecule 1 (IBA-1), as the marker of microglia activation, and IL-1ß were assessed. METHODS: Adult male NMRI mice were treated with Al-NP (5 or 10 mg/kg) for 5 days. A novel object recognition (NOR) test was used to assess memory. Following cognitive assessments, the hippocampal tissues were isolated to analyze the levels of IL-1ß and IBA-1 as well as beta actin proteins using western blot technique. RESULTS: Al-NP in both doses of 5 and 10 mg/kg impaired NOR memory in mice. In addition, Al-NP increased IL-1ß and IBA-1 in the hippocampus. DISCUSSION: These findings indicate that the memory impairing effect of Al-NP coincides with hippocampal inflammation. According to the proposed relationship between AD and Al toxicity, this study can increase the knowledge about the toxic effects of Al-NP and highlight the need to limit the use of this nanoparticle.
Asunto(s)
Aluminio , Enfermedad de Alzheimer , Humanos , Ratones , Masculino , Animales , Aluminio/toxicidad , Aluminio/metabolismo , Regulación hacia Arriba , Hipocampo , Enfermedad de Alzheimer/metabolismo , Interleucina-1beta/metabolismo , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Inflamación/metabolismo , Microglía/metabolismoRESUMEN
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disease characterized by brain cholinergic dysfunction. Evidence suggests the impairment of memory retrieval phase in AD. It has been shown that CaMKII-α expressing neurons are selectively reduced in the hippocampus in AD brains. The present study aimed to investigate the effect of scopolamine on the memory retrieval phase and the hippocampal CaMKII-α signaling. In addition, the effect of sub-chronic administration of agmatine against scopolamine induced memory and possible hippocampal CaMKII-α deregulation was investigated in mice. Adult male NMRI mice were administered with agmatine at the doses of 5, 10, 20, 30 and 40 mg/kg/i.p. or saline for 11 days. Acquisition and retrieval tests of passive avoidance task were performed on days 10 and 11, respectively (30 Min following agmatine treatment). Scopolamine (1 mg/kg/i.p.) was administered once, 30 Min before retrieval test. Upon completion of the behavioral tasks, the hippocampi were isolated for western blot analysis to detect the phosphorylated and total levels of CaMKII-α and beta actin proteins. The results showed that scopolamine induced memory retrieval deficit and decreased the phosphorylated level of hippocampal CaMKII-α. Sub-chronic agmatine treatment at the dose of 40 mg/kg prevented scopolamine induced memory retrieval deficit and restored the level of hippocampal phosphorylated CaMKII-α. This study suggests that hippocampal CaMKII-α might play a role in scopolamine induced amnesia and sub-chronic agmatine prevents the impairing effect of scopolamine on the retrieval phase of memory and the phosphorylation of hippocampal CaMKII-α protein.
Asunto(s)
Agmatina , Enfermedades Neurodegenerativas , Ratones , Masculino , Animales , Agmatina/farmacología , Agmatina/uso terapéutico , Agmatina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Hipocampo , EscopolaminaRESUMEN
The growing usage of aluminum nanoparticles (Al-NP) and their exposure may influence body function. Considering the proposed relationship between Al and the pathogenesis of Alzheimer's disease and the concern about the effect of this nanoparticle on brain health and cognitive function, the use of neuroprotective agents might be helpful. According to the reported neuroprotective effects of agmatine, in the present study, the possible protective effect of agmatine was assessed in mice model of Al-NP-induced memory impairment. In addition, due to the roles of hippocampal Glycogen synthase kinase-3 beta (GSK-3ß) and ERK signaling in memory and its disorders, these pathways were also investigated. Al-NP (10â mg/kg/p.o.) with/without agmatine (5 or 10â mg/kg/i.p.) was administered to adult male NMRI mice for 5 days. Novel object recognition (NOR) test session was used to assess cognitive function. Following the behavioral assessments, the hippocampi were used to determine the phosphorylated and total levels of GSK-3ß and ERK as well as GAPDH using western blot analysis. The results showed that Al-NP impaired NOR memory in mice while agmatine 10â mg/kg prevented the memory deficit induced by Al-NP. Furthermore, Al-NP activated GSK-3ß as well as ERK signals within the hippocampus while agmatine prevented the effects of Al-NP on GSK-3ß and ERK signals within the hippocampus. Besides supporting the neuroprotective effects of agmatine, these findings suggest the possibility of the connection of hippocampal GSK-3ß and ERK signaling in the neuroprotective effect of this polyamine against Al-NP.
Asunto(s)
Agmatina , Fármacos Neuroprotectores , Ratones , Masculino , Animales , Agmatina/farmacología , Aluminio/toxicidad , Aluminio/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fármacos Neuroprotectores/farmacología , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/prevención & control , HipocampoRESUMEN
Agmatine is a polyamine suggested to act as a supposed neurotransmitter in the brain. Evidence has indicated that acute agmatine administration might modulate memory. The present study aimed to investigate the effect of repeated agmatine treatment on passive avoidance memory, hippocampal calcium-calmodulin-dependent protein kinase II-alpha (CaMKII-α), and Extracellular Signal-Regulated Kinase (ERK) signaling pathways in naive mice. Adult male NMRI mice were treated with agmatine (10, 20, 30, 40, and 80 mg/kg/ip) or saline for 11 days. Acquisition and retention tests of passive avoidance memory were performed on days 10 and 11, respectively. Following the memory retention test, the hippocampi were assessed for the levels of CaMKII-α and ERK using the western blotting technique. The results revealed the dose-dependent effect of agmatine on the passive avoidance memory. Accordingly, the memory was impaired in lower doses, but was improved in higher ones. Agmatine in none of the doses affected the nociception of the mice in tail-flick test. Furthermore, agmatine increased the phosphorylation of CaMKII-α and ERK in the hippocampus at memory enhancing doses, while ERK phosphorylation decreased following the impairing doses of agmatine. Thus, the dose-dependent effect of agmatine on memory might be related to its modulatory effect on CaMKII-α and ERK signal transduction, eventually regulating the memory process.
Asunto(s)
Agmatina , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Agmatina/metabolismo , Agmatina/farmacología , Animales , Reacción de Prevención , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipocampo , Masculino , Ratones , Fosforilación , Transducción de SeñalRESUMEN
Renal ischemia/reperfusion (I/R) injury is considered as a main problem in clinical practice. Curcuminoids, the active constituents of turmeric, seem to have potential renoprotective effects. However, the poor bioavailability of curcuminoids restricts their therapeutic effects. In the present study, the effect of nanomicellar curcuminoids (NC) treatment on renal function, histology, total antioxidant capacity (TAC), total oxidative stress (TOS), caspase-3 level as well as mitogen activated protein kinases (MAPKs: JNK, p38 and ERK) phosphorylation were evaluated following renal I/R. Adult male Sprague-Dawley rats were administered NC at the dose of 25 mg/kg 1 h before renal ischemia induction. The animals were subjected to bilateral renal ischemia for 60 min and reperfusion for 24 h. Subsequently, blood urea nitrogen (BUN), creatinine (Cr), renal histopathology, TAC, TOS, and oxidative stress index, cleaved caspase-3 level, Bax and MAPKs signaling were evaluated. The results indicated that NC pretreatment at the dose of 25 mg/kg significantly improved renal function as well as histolopatholgical damages. Moreover, NC reduced the level of renal oxidative stress, cleaved caspase-3 and Bax (as the proapoptotic proteins) and suppressed the activated Jun N-terminal Kinase (JNK), p38 and extracellular receptor kinase (ERK) signaling induced by renal I/R. The findings of the current study indicate that NC might prevent the injury induced by renal I/R through suppression of oxidative stress, apoptosis and MAPKs pathways.
Asunto(s)
Apoptosis/efectos de los fármacos , Diarilheptanoides/farmacocinética , Riñón/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Nanopartículas/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Nitrógeno de la Urea Sanguínea , Caspasa 3/metabolismo , Creatinina/sangre , Diarilheptanoides/administración & dosificación , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Riñón/metabolismo , Riñón/fisiopatología , Sistema de Señalización de MAP Quinasas/genética , Masculino , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/fisiopatología , Proteína X Asociada a bcl-2/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Caffeine, one of the most widely consumed psychoactive substance in the world, has been shown to affect mood, memory, alertness, and cognitive performance. This study aimed to assess the effect of sub-chronic oral gavage of caffeine on memory and the phosphorylation levels of hippocampal Akt (protein kinase B), GSK-3ß (Glycogen Synthase Kinase-3beta) and ERK (extracellular signal-regulated kinase) in mice. Adult male NMRI mice were administered with caffeine at the doses of 0.25, 0.5, 0.75 and 1.5 mg/kg/oral gavage for 10 days before behavioral assessments. Upon completion of the behavioral tasks, the hippocampi were isolated for western blot analysis to detect the phosphorylated and total levels of Akt, GSK-3ß and ERK proteins. The results showed that sub-chronic caffeine ingestion at the dose of 0.5 mg/kg improves memory in mice both in passive avoidance and novel object recognition tasks. Furthermore, this memory enhancing dose of caffeine elevated the ratios of phosphorylated to total contents of hippocampal Akt, GSK-3ß and ERK. This study suggests that sub-chronic low dose of caffeine improves memory and increases the phosphorylation of hippocampal Akt, GSK-3ß and ERK proteins.
Asunto(s)
Cafeína/farmacología , Hipocampo/efectos de los fármacos , Memoria/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hipocampo/metabolismo , Masculino , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Objectives: Cholinergic system dysfunction was found to play a key role in Alzheimer's disease (AD) pathogenesis. Therefore, the animal model of scopolamine-induced amnesia has been widely used in AD researches. Cinnamon, as a spice commonly used in cuisine, has been shown to exert some therapeutic effects. The most abundant compound in cinnamon is cinnamaldehyde which recently was shown to exert several neuroprotective effects in animal models. Therefore, this study aimed to assess whether cinnamaldehyde has the potency to prevent memory retrieval impairment and hippocampal protein kinase B (Akt) and MAPK (extracellular signal-regulated kinase (ERK)) alterations induced by scopolamine in mice.Methods: Adult male mice were pretreated with cinnamaldehyde (12.5, 25, 40 and 100 mg/kg/oral gavage) 10 days before training. The training of passive avoidance task was performed on the 10th day and a memory retention test was done 24 h later. Scopolamine (1 mg/kg) was injected intraperitoneally, 30 min before the retention test to induce memory retrieval deficit. At the complement of the behavioral experiments, the hippocampi were isolated for western blot analysis to assess the phosphorylated and total levels of hippocampal MAPK and Akt proteins.Results: The results showed that cinnamaldehyde pretreatment at the dose of 100 mg/kg significantly prevented the amnesic effect of scopolamine. Furthermore, cinnamaldehyde prevented scopolamine induced dysregulations of hippocampal MAPK and Akt.Discussion: The results of the present study revealed that oral sub-chronic cinnamaldehyde administration has the capability to prevent memory retrieval deficit induced by cholinergic blockade and restores hippocampal MAPK and Akt dysregulations.
Asunto(s)
Acroleína/análogos & derivados , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipocampo/metabolismo , Trastornos de la Memoria/prevención & control , Proteínas Proto-Oncogénicas c-akt/metabolismo , Escopolamina/efectos adversos , Acroleína/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Trastornos de la Memoria/inducido químicamente , Ratones , FosforilaciónRESUMEN
Cinnamon, a spice widely used in cuisine, has been reported to exert therapeutic effects. Recently, cinnamon was shown to improve memory in some animal models of memory impairment and in poor learning mice. This study aimed to investigate the effect of cinnamaldehyde, the major compound in cinnamon on passive avoidance memory and activation of hippocampal Akt (protein kinase B), ERK (extracellular signal-regulated kinase) and GSK-3ß (Glycogen Synthase Kinase-3beta) in mice. In the present study, oral cinnamaldehyde at doses of 12.5, 25, 30, 40, 45, 50 and 100â¯mg/kg/daily was administered to adult male NMRI mice, initiated 10 days before training and continued during training and retention days. Training of passive avoidance task was performed on day 10 and a retention trial was done 24â¯h after. Upon completion of the retention test, hippocampi were removed for Western blot analysis to detect the phosphorylated and total levels of Akt, ERK and GSK-3ß proteins. Results showed that cinnamaldehyde exerts a biphasic effect on passive avoidance memory by impairing memory at lower doses while improving at higher doses. Moreover, at memory improving doses, cinnamaldehyde increased the phosphorylated forms of hippocampal Akt, ERK and GSK-3ß while these proteins did not change at impairing doses of cinnamaldehyde. For the first time, this study revealed a biphasic effect of cinnamaldehyde on memory as well as indicating that the memory improving effect of higher doses of this substance is accompanied with hippocampal Akt, ERK and GSK-3ß signaling alterations in adult mice.
Asunto(s)
Acroleína/análogos & derivados , Reacción de Prevención/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hipocampo/efectos de los fármacos , Memoria/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Acroleína/farmacología , Animales , Relación Dosis-Respuesta a Droga , Hipocampo/metabolismo , Hipocampo/fisiología , Masculino , Ratones , Fosforilación/efectos de los fármacosRESUMEN
INTRODUCTION: There is evidence indicating that the rate of AD is lower in curry consuming populations. Then, there is an effort to elucidate if curcumin -as the main ingredient of turmeric-might affect the process of AD. However, in clinical trials of AD, a six-month curcumin treatment failed to show any progress, which might be attributable to its low bioavailability. In this line, a recent human study revealed that a more bioavailable solid lipid curcumin enhances cognition in aged adults. By the application of Bovine Serum Albumin (BSA), the current study aimed at converting curcumin to nano sizes and assessing its protective effects against scopolamine-induced passive avoidance memory retrieval deficit. METHODS: Nanocurcumin was prepared via dissolution method. Male NMRI mice (20-25 g body weight) were used. The effective doses of nanocurcumin were selected according to the initial pilot test. The mice were treated with nanocurcumin 15 or 20 mg/kg/p.o or distilled water for 10 days. The animals were habituated and trained in passive avoidance apparatus on the day 10. The retention test was performed 24 hours later. Scopolamine (1 mg/kg/i.p.) or saline was injected 30 minutes before memory retention trial. RESULTS: The findings indicated that nanocurcumin in doses 15 or 20 mg/kg/p.o prevented the retrieval deficit induced by scopolamine while natural curcumin in its equivalent doses did not have such an effect. Furthermore, nanocurcumin by itself improved memory retention comparing with the control group. CONCLUSION: These findings implied that the potential anti-amnesic effects of curcumin might be observed by producing and using its nanoformulation form.
RESUMEN
The loss of cholinergic neurons has been a major issue in researches on Alzheimer's disease (AD) for about 40 years. Therefore, the scopolamine model of amnesia has been widely used in AD researches. Recently, it was reported that the early stage amnesia of AD is related to memory retrieval deficit. Curcumin, as the main ingredient of turmeric, has been suggested to decrease the prevalence of AD in human population. This study was conducted to assess if curcumin prevents retrieval deficit induced by scopolamine in passive avoidance task. Moreover, according to the proposed link between cholinergic system and Akt/GSK-3ß (Glycogen synthase kinase 3 beta) signaling, the hippocampal contents of these proteins were determined. Male NMRI mice (20-25â¯g body weight) were treated with 50 or 100â¯mg/kg/po curcumin or its vehicle for 10 days. On day 10, the animals were trained in passive avoidance apparatus. The retention trial was performed 24â¯h later. Scopolamine (1â¯mg/kg/i.p.) or its vehicle was administered 30â¯min before retention test. At the completion of behavioral studies, the hippocampi were removed and western blot analysis was performed to determine hippocampal phosphorylated and total Akt and GSK-3ß and beta actin contents. The results showed that curcumin treatment at 50 and 100â¯mg/kg doses prevented scopolamine-induced memory retrieval deficit and restored Akt and GSK dephosphorylation caused by scopolamine. Overall, these findings showed that pre-test scopolamine administration disrupts memory retrieval along with the diminished Akt and GSK-3ß phosphorylation in hippocampus while curcumin administration prevented those changes.
Asunto(s)
Curcumina/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hipocampo/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/fisiopatología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Escopolamina/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Curcumina/uso terapéutico , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Trastornos de la Memoria/metabolismo , Ratones , Fosfoproteínas/metabolismoRESUMEN
Although high rate of curcumin consumption has been suggested to decrease the prevalence of Alzheimer's disease (AD), its administration has no effect on the progression of AD in humans and this has been attributed to its poor bioavailability. Using nanotechnology to break down curcumin increases its bioavailability and improves its effect on the brain. BSA, as a non-toxic protein with high binding capacity, was used to break curcumin to nanosize and to explore the effect of nanocurcumin on passive avoidance memory and hippocampal MMP-2 and -9 and MAPKs. BSA-based nanocurcumin was produced by desolvation method. In this study, 15 and 20 mg/kg/p.o. nanocurcumin (based on our preliminary studies) were administered to male NMRI mice weighing 20-25 g for 10 days. Passive avoidance training was performed on day 10 and 24 h after, a retention trial was done. Upon completion of behavioral studies, the hippocampi were isolated and western blot analysis was performed on MMP-2, MMP-9, and MAPKs (JNK, ERK, and p38). The results showed that BSA-based nanocurcumin administered at 15 and 20 mg/kg doses resulted in a significantly improved performance in passive avoidance memory test while its equivalent doses of natural curcumin did not produce a similar effect. In addition, this effect was accompanied with an increase in MMP-2, MMP-9, and p-ERK and a decrease in p-JNK. This study indicates that breaking curcumin to nanosize produces improved effects on passive avoidance memory in adult mice accompanied with MMP-2, MMP-9, p-ERK, and p-JNK changes in the hippocampus.
Asunto(s)
Curcumina/farmacología , Hipocampo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Memoria , Nanopartículas/química , Albúminas/química , Animales , Curcumina/administración & dosificación , Hipocampo/metabolismo , Hipocampo/fisiología , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , RatonesRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognitive deficit. The observed amnesia in the early stages of AD is suggested to be a retrieval problem, rather than encoding and consolidation deficit. According to the cholinergic hypothesis of AD, scopolamine is used to induce an animal model of amnesia. Howbeit the effect of scopolamine on memory retrieval is contradictory. This study aimed to assess the effect of scopolamine on passive avoidance memory retrieval. Additionally according to the reported changes of MMP-2, MMP-9 and MAPKs (ERK, P38 and JNK) in AD pathology the hippocampal contents of these proteins were determined. Male NMRI mice weighing 20-25g were trained in passive avoidance apparatus. The drug or its vehicle was injected 24h after training (30min before retention test). The hippocampal tissue was isolated and western blot analysis was done for MMP-2, MMP-9 and MAPKs (ERK, P38 and JNK). The results indicated that scopolamine (1mg/kg) disrupts passive avoidance memory retrieval. This scopolamine treatment resulted in hippocampal MMP-2 and MMP-9 decline while increased MAPKs in the hippocampus. These results suggest that cholinergic system has an important role in learnt memory retrieval. It might also suggest the positive role of MMP-2 and MMP-9 in this phase of memory while propose that MAPKs affect negatively the reactivation of memory which is compatible with MAPKs activation in AD.